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1. Several studies on monozygotic twins discordant for schizophrenia showed that the cerebral ventricle-brain ratio (VBR) was larger in the twins with schizophrenia, as compared with the corresponding normal twins. 2. The results suggest that the difference of the VBR of the discordant twins was larger than that of the concordant twins of schizophrenia. 3. The authors studied the VBR in four monozygotic twin pairs discordant and four monozygotic twin pairs concordant for schizophrenia by computerized tomography. 4. In the discordant twins, all pairs showed that the VBR of the normal twins was smaller than that of the corresponding twins with schizophrenia. 5. The difference of the VBR of the discordant twins and that of the concordant twins of schizophrenia was not statistically different using Mann-Whitney U test. 6. The preliminary results suggest that the VBR enlargement in schizophrenia is not genetically controlled in monozygotic twins either discordant or concordant for schizophrenia. 7. In monozygotic concordant twins, the brain pathology may be heterogeneous.

Anticipation, i.e., a decrease in the age of onset and/or an increase in the severity of a disease in subsequent generations, and imprinting, i.e., different modes of parental transmission, have been suggested in trinucleotide repeat amplification diseases. The purpose of this study was to determine if anticipation and imprinting are associated with familial schizophrenia. Two generations of 49 schizophrenics from 24 families were studied. Ages of onset, numbers hospitalized, diagnostic subclasses of schizophrenia, amounts of antipsychotics, positive symptoms, negative symptoms, treatment resistance, and clinical course ratings, were compared between the two generations. The age of onset was significantly lower in the offspring generation, although there was no difference in the severity between the two generations. The negative symptom scores and clinical course scores in the offspring generation for paternal transmission were significantly higher than those for maternal transmission. Our results suggest the presence of imprinting and anticipation in schizophrenia.

Trinucleotide repeat expansion diseases are characterized by anticipation. Several studies suggested the anticipation in schizophrenia. We studied five novel trinucleotide repeats identified by Li et al in a human brain cDNA library in 100 unrelated control subjects, and 57 subjects in 17 families with schizophrenia. The CTG-B43 and B45d, and CCG-A3 were not polymorphic in any unrelated control subjects or subjects with familial schizophrenia. The CTG-A4 had two alleles and the CTG-B1 three alleles. The two clones were not expanded in subjects with familial schizophrenia or unrelated healthy controls. There was no difference in allele frequency between unrelated control subjects and subjects in the families with schizophrenia. The allele frequencies in unaffected and affected subjects in the families with schizophrenia were not significantly different. There was no difference between the offspring and parental generations of affected subjects in the families with schizophrenia. The results suggest the exclusion of the five trinucleotide repeat expansions in the 17 families with schizophrenia.

Since 1991, more than five neuro-genetic disorders have been recognized to be caused by trinucleotide repeat expansions, and the list of such disease should grow. The diseases are characterized clinically by the phenomenon of anticipation, i.e., worsening of the disease phenotype in successive generations with increasing trinucleotide repeat expansion. The presence of anticipation in familial schizophrenia has been suggested. Several studies have provided supportive evidence that the suceptability locus for schizophrenia is on chromosome 6. Therefore, we analyzed three CAG trinucleotide repeat clones D6S1014, D6S1015, and D6S1058 on chromosome 6, which are polymolphic in 30 families with schizophrenia. No unusually, long alleles that would suggest abnormal expansion of more than 35 trinucleotide repeats were observed for these genes. Also, no statistically significant differences were found between the offspring and parental generations of affected subjects or between the affected and unaffected subjects in families with schizophrenia.